Endocrine and Local IGF-I in the Bony Fish Immune System.

A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived), which has also been shown to be suppressed during infection in some studies.

Mutagenesis of lysines 156 and 159 in human immunodeficiency virus type 1 integrase (IN) reveals differential interactions between these residues and different IN inhibitors.

Human immunodeficiency virus (HIV) type I integrase (IN) active site, and viral DNA-binding residues K156 and K159 are predicted to interact both with strand transfer-selective IN inhibitors (STI), e.g. L-731,988, Elvitegravir (EVG), and the FDA-approved IN inhibitor, Raltegravir (RGV), and strand transfer non-selective inhibitors, e.

Oestrogen and insulin-like growth factors during the reproduction and growth of the tilapia Oreochromis niloticus and their interactions.

Oestrogens and insulin-like growth factors (Igfs) play both a central role in the regulation of reproduction and growth and can interact especially in species showing a clear-cut sex-linked growth dimorphism (SGD) like in tilapia. Aromatase is essential in ovarian differentiation and oogenesis since it controls oestrogen synthesis. During tilapia sex differentiation, aromatase cyp19a1a expression increases from 9 days post-fertilization (dpf), resulting in high oestradiol level.

Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells.

Exercise, obesity and type 2 diabetes are associated with elevated plasma concentrations of interleukin-6 (IL-6). Glucagon-like peptide-1 (GLP-1) is a hormone that induces insulin secretion. Here we show that administration of IL-6 or elevated IL-6 concentrations in response to exercise stimulate GLP-1 secretion from intestinal L cells and pancreatic alpha cells, improving insulin secretion and glycemia.

Design, synthesis, and biological evaluation of novel hybrid dicaffeoyltartaric/diketo acid and tetrazole-substituted L-chicoric acid analogue inhibitors of human immunodeficiency virus type 1 integrase.

Fourteen analogues of the anti-HIV-1 integrase (IN) inhibitor L-chicoric acid (L-CA) were prepared. Their IC(50) values for 3'-end processing and strand transfer against recombinant HIV-1 IN were determined in vitro, and their cell toxicities and EC(50) against HIV-1 were measured in cells (ex vivo). Compounds 1-6 are catechol/β-diketoacid hybrids, the majority of which exhibit submicromolar potency against 3'-end processing and strand transfer, though only with modest antiviral activities.

Seawater and freshwater challenges affect the insulin-like growth factors IGF-I and IGF-II in liver and osmoregulatory organs of the tilapia.

Contradictory studies suggest IGF-I in fish liver and gills is involved in osmoregulation, but nothing is known about the kidney and intestine's role nor about IGF-II's role in any organ. Tilapia were transferred from freshwater (FW) to seawater (SW) for 1week (wk) and retransferred to FW for another week. At 4h, 1d, 2d, 3d and 1wk after SW-transfer and FW-retransfer IGF-I, IGF-II and growth hormone receptor (GHR1) mRNA were measured by real-time PCR.

Anti-tuberculosis compounds from Mallotus philippinensis.

Bioassay-directed fractionation of the organic extract of Mallotus philippinensis gave five compounds (1-5), the most active of which against Mycobacterium tuberculosis was a new compound, 8-cinnamoyl-5,7-dihydroxy-2,2-dimethyl-6-geranylchromene (1) for which the name mallotophilippen F is suggested. Compound (2), 8-cinnamoyl-2,2-dimethyl-7-hydroxy-5-methoxychromene, was isolated from a natural source for the first time, while the remaining three compounds, rottlerin (3), isoallorottlerin=isorottlerin (4) and the so-called "red compound," 8-cinnamoyl-5,7-dihydroxy-2,2,6-trimethylchromene (5), had been isolated previously from this plant. All compounds were identified by analysis of their spectra including 2D-NMR, which was used to correct the literature NMR spectral assignments of compounds 2-4.

Insulin-like growth factor-3 (IGF-3) in male and female gonads of the tilapia: development and regulation of gene expression by growth hormone (GH) and 17alpha-ethinylestradiol (EE2).

Recently, in addition to IGF-1 and IGF-2 the existence of a third form of IGF, termed IGF-3, limited to fishes, to be present only in the gonads and encoded by a separate gene has been reported. However, no further data have been presented on IGF-3. The present study on tilapia (Oreochromis niloticus) uses quantitative real-time PCR specific for tilapia IGF-1 and IGF-3.

Insulin-like growth factors and fish reproduction.

Knowledge of fish reproduction is of high relevance to basic fish biology and comparative evolution. Furthermore, fish are excellent biomedical models, and the impact of aquaculture on worldwide food production is steadily increasing. Consequently, research on fish reproduction and the potential modes of its manipulation has become more and more important.

Distinct organ-specific up- and down-regulation of IGF-I and IGF-II mRNA in various organs of a GH-overexpressing transgenic Nile tilapia.

Several lines of GH-overexpressing fish have been produced and characterized concerning organ integrity, growth, fertility and health but few and contradictory data are available on IGF-I that mediates most effects of GH. Furthermore, nothing is known on IGF-II. Thus, the expression of both IGFs in liver and various extrahepatic sites of adult transgenic (GH-overexpressing) tilapia and age-matched wild-type fish was determined by real-time PCR.

Environmentally relevant concentrations of 17alpha-ethinylestradiol (EE2) interfere with the growth hormone (GH)/insulin-like growth factor (IGF)-I system in developing bony fish.

The aim of this study was to evaluate whether effects of environmental estrogens on fish growth and reproduction may be mediated via modulating the growth hormone (GH)/insulin-like growth factor I (IGF-I) system. To this end, developing male and female monosex populations of tilapia were exposed to 17alpha-ethinylestradiol (EE2) at 5 and 25 ng EE2/l water from 10-day postfertilization (DPF) until 100 DPF. Under exposure to both EE2 concentrations, sex ratio shifted toward more females and body length, and weight were significantly reduced in males.

Ethinylestradiol differentially interferes with IGF-I in liver and extrahepatic sites during development of male and female bony fish.

Growth and sexual development are closely interlinked in fish; however, no reports exist on potential effects of estrogen on the GH/IGF-I-axis in developing fish. We investigate whether estrogen exposure during early development affects growth and the IGF-I system, both at the systemic and tissue level. Tilapia were fed from 10 to 40 days post fertilization (DPF) with 17alpha-ethinylestradiol (EE(2)).

Increased number of islet-associated macrophages in type 2 diabetes.

Activation of the innate immune system in obesity is a risk factor for the development of type 2 diabetes. The aim of the current study was to investigate the notion that increased numbers of macrophages exist in the islets of type 2 diabetes patients and that this may be explained by a dysregulation of islet-derived inflammatory factors. Increased islet-associated immune cells were observed in human type 2 diabetic patients, high-fat-fed C57BL/6J mice, the GK rat, and the db/db mouse.

Insulin-like growth factor I (IGF-I) in a growth-enhanced transgenic (GH-overexpressing) bony fish, the tilapia (Oreochromis niloticus): indication for a higher impact of autocrine/paracrine than of endocrine IGF-I.

Several lines of growth hormone (GH)-overexpressing fish have been produced and analysed for growth and fertility parameters. However, only few data are available on the growth-promoting hormone insulin-like growth factor I (IGF-I) that mediates most effects of GH, and these are contradictory. Using quantitative real-time RT-PCR, radioimmunoassay, in situ hybridization, immunohistochemistry, and radiochromatography we investigated IGF-I and IGF binding proteins (IGFBPs) in an adult (17 months old) transgenic (GH-overexpressing) tilapia (Oreochromis niloticus).

Hypoglycemia due to paraneoplastic secretion of insulin-like growth factor-I in a patient with metastasizing large-cell carcinoma of the lung.

Context: Nonpancreatic tumors may cause recurrent hypoglycemia known as nonislet cell tumor hypoglycemia. It is due to overproduction and secretion by the tumor of incompletely processed IGF-II, termed big IGF-II. We recently identified a patient with recurrent hypoglycemia and low insulin, but without elevated big IGF-II.

Insulin-like growth factor I (IGF-I) and its receptor (IGF-1R) in the rat anterior pituitary.

Few and controversial results exist on the cellular sites of insulin-like growth factor (IGF)-I synthesis and the type 1 IGF receptor (IGF-1R) in mammalian anterior pituitary. Thus, the present study analysed IGF-I and the IGF-1R in rat pituitary. Reverse transcription-polymerase chain reaction revealed IGF-I and IGF-1R mRNA expression in pituitary.

IGF-I is distinctly located in the bony fish pituitary as revealed for Oreochromis niloticus, the Nile tilapia, using real-time RT-PCR, in situ hybridisation and immunohistochemistry.

In bony fish, IGF-I released from the liver under the control of pituitary GH is the main endocrine regulator of growth, maintenance and development, and the amount of circulating IGF-I regulates synthesis and release of GH. In mammals and amphibia, evidence indicates that anterior pituitary endocrine cells also contain IGF-I. However, only preliminary and conflicting data exist on IGF-I gene expression in bony fish pituitary.

Organ-specific expression of IGF-I during early development of bony fish as revealed in the tilapia, Oreochromis niloticus, by in situ hybridization and immunohistochemistry: indication for the particular importance of local IGF-I.

The cellular sites of insulin-like growth factor I (IGF-I) synthesis in the early developing tilapia (0-140 days post fertilization, DPF) were investigated. IGF-I mRNA and peptide appeared in liver as early as 4 DPF and in gastro-intestinal epithelial cells between 5-9 DPF. In exocrine pancreas, the expression of IGF-I started at 4 DPF and continued until 90 DPF.

A systematic immunohistochemical survey of the distribution patterns of GH, prolactin, somatolactin, beta-TSH, beta-FSH, beta-LH, ACTH, and alpha-MSH in the adenohypophysis of Oreochromis niloticus, the Nile tilapia.

Fish pituitary plays a central role in the control of growth, development, reproduction and adaptation to the environment. Several types of hormone-secreting adenohypophyseal cells have been characterised and localised in diverse teleost species. The results suggest a similar distribution pattern among the species investigated.

Differential expression of IGF-I mRNA and peptide in the male and female gonad during early development of a bony fish, the tilapia Oreochromis niloticus.

Insulin-like growth factor I (IGF-I) plays a key role in the complex system that regulates bony fish growth, differentiation, and reproduction. The major source of circulating IGF-I is liver, but IGF-I-producing cells also occur in other organs, including the gonads. Because no data are available on the potential production sites of IGF-I in gonad development, developmental stages of monosex breedings of male and female tilapia from 0 day postfertilization (DPF) to 90 DPF were investigated for the production sites of IGF-I at the peptide (immunohistochemistry) and mRNA (in situ hybridization) level.

Mechanisms of beta-cell death in type 2 diabetes.

A decrease in the number of functional insulin-producing beta-cells contributes to the pathophysiology of type 2 diabetes. Opinions diverge regarding the relative contribution of a decrease in beta-cell mass versus an intrinsic defect in the secretory machinery. Here we review the evidence that glucose, dyslipidemia, cytokines, leptin, autoimmunity, and some sulfonylureas may contribute to the maladaptation of beta-cells.

A survey on the expression of IGF-I in the early developing bony fish with special emphasis on the tilapia, Oreochromis niloticus.

The present study investigates the expression of IGF-I in the early developing tilapia (Oreochromis niloticus). IGF-I was detected very early in ontogeny (4-5 days postfertilization, DPF), first in liver and in organs involved in growth and metabolism, thus suggesting a high physiological impact of IGF-I in growth, metabolism, and organogenesis.

The advantage of absolute quantification in comparative hormone research as indicated by a newly established real-time RT-PCR: GH, IGF-I, and IGF-II gene expression in the tilapia, Oreochromis niloticus.

We have developed a real-time RT-PCR that absolutely quantifies the gene expression of hormones using the standard curve method. The method avoids cloning procedures by using primer extension to create templates containing a T7 promoter gene sequence. It is rapid since neither separate reverse transcriptions nor postamplification steps are necessary, and its low detection level (2 pg/mug total RNA) allows precise absolute quantification.

Expression of endogenous and exogenous growth hormone (GH) messenger (m) RNA in a GH-transgenic tilapia (Oreochromis niloticus).

We have previously produced transgenic fish from crosses between a wild-type female tilapia (Oreochromis niloticus) and a G transgenic male. This line of growth-enhanced tilapia carries a single copy of a chinook salmon (s) growth hormone (GH) gene spliced to an ocean pout antifreeze promoter (OPA-FPcsGH) co-ligated to a carp beta-actin/lacZ reporter gene construct, integrated into the tilapia genome. Because little is known about the expression sites of transgenes, we have characterised the gene expression patterns of sGH and tilapia (t)GH in transgenic tilapia using a newly established real-time PCR to measure the absolute mRNA amounts of both hormones.

Growth hormone and insulin-like growth factors in fish: where we are and where to go.

This communication summarizes viewpoints, discussion, perspectives, and questions, put forward at a workshop on "Growth hormone and insulin-like growth factors in fish" held on September 7th, 2004, at the 5th International Symposium on Fish Endocrinology in Castellon, Spain.